Discussion:
Due to the semi-allograft nature of the fetus in utero, the immune
response requires both stimulatory and suppressive functions for a
successful pregnancy outcome. Lymphocytes are a contributor in the
maternal immunological response to pregnancy. The normal lymphocyte
count changes in pregnancy, and there is no consensus in the literature
about how it changes. Some older papers suggest that there was no change
overall in lymphocyte count during pregnancy (13,14). Results from more
recent studies suggest that there is a decrease in lymphocyte count
(15,16), with the biggest decrease occurring in the first and second
trimesters (5). The bulk of available literature agrees with the
findings of a reduction in overall lymphocyte count; however, a recent
study in 2013 found a significant increase in the lymphocyte count of
200 pregnant women (17,18), further complicating the discussion.
Some papers suggested lymphopenia is associated with worse outcomes in
COVID patients. (4) Another study observed that, progressive decline in
the lymphocyte count and rise in the D-dimer over time were observed in
non survivors compared with higher levels in survivors after COVID-19
infections (5).The same authors observed that common laboratory findings
among hospitalized patients with COVID-19 include lymphopenia, elevated
aminotransaminase levels, elevated lactate dehydrogenase levels, and
elevated inflammatory markers (e.g., ferritin, C-reactive protein, and
erythrocyte sedimentation rate) (5)
In a series of 393 adult patients hospitalized with COVID-19 in New York
, 90 % had a lymphocyte count <1500/microL; leukocytosis
(>10,000/microL) and leukopenia (<4000/microL) in
15% of cases(6)
Another study showed that high D-dimer levels and marked lymphopenia,
are associated with higher mortality rate. (7) A retrospective analysis
of eight pregnant cases of SARS-CoV-2 showed that 50% were asymptomatic
before delivery but became symptomatic post-partum. This was associated
with ,raised white blood cell counts , and reduced lymphocyte counts.
C-reactive protein levels increased (8).
In another contradicting cohort study of 55 patients who gave birth
with suspected COVID -19 disease of which 13 later turned out positive
to COVID-19, there was no difference in the WBC, the ratio of the
neutrophils and lymphocytes, CRP between both suspected and confirmed
cases groups.(9)
Another study observed that in COVID-19 positive cases there was
abnormalities on chest imaging, lymphopenia, leukopenia, and
thrombocytopenia. (10)
A meta-analysis of 33 studies reporting 385 pregnant women with COVID-19
infection: noted 0.8% critical, 3.6% severe infection, 95.6% with
mild symptoms. There were 6 women admitted to intensive care and one
maternal mortality. Laboratory findings included elevated D-dimer in
(22.3%), elevated C-reactive protein in (18.7%), lymphopenia in
(14.0%), and thrombocytopenia in (1.0%) women. (11)
In another meta-analysis, lymphopenia was found in 79.8% (40/48) of
cases. Also, it was reported that radiological features suggestive for
pneumonia could be found in almost all of the hospitalized pregnant
women, usually presenting with fever, cough and lymphopenia similar to
the non-pregnant population. (12)
A recent meta-analysis with 828 patients, where 407 patients had severe
disease (49.15%) concluded that the NLR values were found to increase
significantly in patients with COVID‐19 with severe disease
(SMD = 2.404, 95% CI = 0.98‐3.82) Increased NLR levels reflect an
enhanced inflammatory process and may suggest a poor prognosis. (20).
Coronavirus mainly act on lymphocytes, especially T lymphocytes.
Surveillance of NLR and lymphocyte subsets helps in screening for
critical cases of COVID-19. A trial with 452 patients with COVID-19 ,
286 were diagnosed with severe infection. Severe cases tend to have
lower lymphocyte counts, and neutrophil-lymphocyte ratio (NLR). The
number of T cells was significantly reduced in severe cases. Both helper
and suppressor T cells in patients with COVID-19 were below normal
levels, with lower levels of Th cells in the severe group. Patients with
COVID-19 also have lower levels of regulatory T cells, which are more
reduced in severe cases. (21)
Neutrophil to lymphocyte ratio (NLR), have been recognized as systemic
inflammatory response (SIR) marker for many years. (22). Research
revealed that NLR offer effective indication of severity of diseases as
pre-eclampsia. NLR, with a cutoff value of 5.6, predicted severe
pre-eclapmsia with sensitivity 93.3% and specificity 86.6% . (23)
Another meta-analysis with 1371 patients showed significantly higher NLR
in non-survivors than in survivors. They also looked at 10,685 patients
evaluating the value of NLR for sepsis prognosis; results showed that
higher NLR was associated with poor prognosis in patients with sepsis .
(24)
Another study looked at NLR as a predictor of mortality and treatment
response in sepsis patients in the intensive care unit (ICU). They
looked at NLR on the 1st, 3rd, and last day in the ICU. If the NLR was
≥15 on the 3rd day, the mortality odds ratio was 6.96 (25)